Controlling the stereochemistry in 2-oxo-aldehyde-derived Ugi adducts through the cinchona alkaloid-promoted electrophilic fluorination.

In this report, we introduce a new strategy for controlling the stereochemistry in Ugi adducts. Instead of controlling stereochemistry directly during the Ugi reaction we have attempted to stereodefine the chiral center at the peptidyl position through the post-Ugi functionalization. In order to achieve this, we chose to study 2-oxo-aldehyde-derived Ugi adducts many of which partially or fully exist in the enol form that lacks the aforementioned chiral center. This in turn led to their increased nucleophilicity as compared to the standard Ugi adducts. As such, the stereocenter at the peptidyl position could be installed and stereodefined through the reaction with a suitable electrophile. Towards this end, we were able to deploy an asymmetric cinchona alkaloid-promoted electrophilic fluorination producing enantioenriched post-Ugi adducts fluorinated at the peptidyl position.

Three-component reaction of azulene, aryl glyoxal and 1,3-dicarbonyl compound for the synthesis of various azulene derivatives.

A three-component reaction of an azulene, an aryl glyoxal and a 1,3-dicarbonyl compound has been elaborated to access a series of azulene derivatives. Some of these azulene-containing adducts were further subjected to post-MCR transformations to assemble azulene-heterocycle conjugates.

Gold-catalyzed post-Ugi alkyne hydroarylation for the synthesis of 2-quinolones.

A series of propargylamides containing an electron-rich benzene ring was prepared through the Ugi reaction of 3,5-dimethoxyaniline with various propiolic acids, aldehydes and isocyanides. Subjecting these adducts to a gold-catalyzed intramolecular alkyne hydroarylation process allowed to efficiently construct the 2-quinolone core bearing a branched substituent on the nitrogen atom.

Gold-Catalyzed Post-Ugi Ipso-Cyclization with Switchable Diastereoselectivity.

A gold-catalyzed post-Ugi ipso-cyclization for the diastereoselective synthesis of spirocyclic pyrrol-2-one-dienone system is described. Tuning the catalytic system, solvent, and temperature allowed selectively attaining two sets of diastereoisomers. The scope of the process has been evaluated, and a putative mechanistic model was proposed.

Reactions of secondary propargylamines with heteroallenes for the synthesis of diverse heterocycles.

This focused review aims to summarize recent developments in the processes involving additions of secondary propargylamines to various heteroallenes and subsequent transition metal-catalyzed or electrophile-mediated cyclizations. The utility of this convenient and tunable strategy spans from the carbon dioxide fixation and target-oriented synthesis of complex natural and biologically active products to the generation of extended synthetic libraries of diverse oxygen-, nitrogen- and sulfur-containing heterocycles. For comparative purposes, the analogous transformations of propargylic alcohols are also highlighted in this account.

Boron Complexes of Glyoxal-Derived Ugi Adducts as a New Class of Aggregation-Induced Emission Photoluminescent Materials.

A series of O,O-chelated boron complexes was prepared through a four-component Ugi reaction followed by complexation of the resulting 1,3-dicarbonyl compounds with boron trifluoride diethyl etherate. The optical properties of these novel luminophores were investigated by UV/Vis spectroscopy and spectrofluorometry, revealing pronounced aggregation-induced emission (AIE) features.

Heck-Suzuki Tandem Reaction for the Synthesis of 3-Benzazepines.

A novel procedure for the Heck-Suzuki tandem reaction suitable for the construction of nitrogen-containing medium rings was developed to provide access toward the 3-benzazepine framework.

Three-component reaction of a 2-aminoazine, a 2-oxoaldehyde, and a cyclic 1,3-dicarbonyl compound for the synthesis of imidazo[1,2-a]azine derivatives.

A three-component reaction of a 2-aminoazine, a 2-oxoaldehyde, and a cyclic 1,3-dicarbonyl compound providing access toward a novel class of imidazo[1,2-a]azine derivatives was developed and studied. The scope of the process was thoroughly explored under three different reaction conditions resulting in the generation of a small library of title compounds and highlighting the possibility of case-specific approach.

Unexpected regio- and chemoselectivity of cationic gold-catalyzed cycloisomerizations of propargylureas: access to tetrasubstituted 3,4-dihydropyrimidin-2(1H)-ones.

Cationic gold-catalyzed cycloisomerizations of propargylureas, derived in situ from secondary propargylamines and aryl or alkyl isocyanates, have been studied. The reaction outcome was found to be different from what was previously observed for the tosyl isocyanate-derived ureas in terms of both regio- and chemoselectivity. As a result, the current protocol offers efficient access to the 3,4-dihydropyrimidin-2(1H)-one core through the 6-endo-dig N-cyclization.

A walk around the A3-coupling.

In recent years, the transition-metal catalyzed three-component coupling of an aldehyde, an alkyne and an amine, commonly called A(3)-coupling, has been established as a convenient and general approach towards propargylamines. Furthermore, the A(3)-coupling has found a broad application as a key step in the construction of various nitrogen-containing heterocycles, biologically active compounds and natural products. Several interesting modifications of the A(3)-coupling as well as different tandem reactions involving A(3)-coupling have been developed. This tutorial review aims to highlight the current achievements in the field of A(3)-couplings and related transformations.

Tetrasubstituted 2-imidazolones via Ag(I)-catalyzed cycloisomerization of propargylic ureas.

A one-pot protocol based on a Ag(I)-catalyzed cycloisomerization of propargylic ureas, derived from secondary propargylamines and isocyanates, was developed for the generation of the 2-imidazolone core.

Unprecedented Cu(I)-catalyzed microwave-assisted three-component coupling of a ketone, an alkyne, and a primary amine.

An efficient, microwave-assisted Cu(I)-catalyzed one-pot coupling of a ketone, an alkyne, and a primary amine (KA(2) coupling) is described, giving access to secondary propargylamines.